Newsletter

[ Vol. 6 No. 3 ] (September - December 2005 )
Optimal safe nutrition in intensive care

Richard D Griffiths
School of Clinical Science, University of Liverpool, and Intensive Care Unit, Whiston Hospital, Merseyside, UK
Email: rdg@liverpool.ac.kr

Optimal Nutrition
General malnutrition or a specific nutrient deficiency has profound effects on outcome and death. Outcome measured by morbidity (such as infection or wound healing) and death are all increased in the ICU patient who is severely malnourished on admission ^[1]and even in patients with multiple organ failure the survival curves start to diverge after 20-30 days ^[2] indicating that outcome should be measured over a longer time frame (e.g six months). Furthermore an increasing nutrition deficit during a long ICU stay is associated with increased morbidity ^[3].

Why might nutrition be so important to the critically ill patient?
The traumatic or septic stressed ICU patient is characterised by increased substrate turnover of carbohydrates, lipids and amino acids, altered inter organ flux coupled with peripheral insulin resistance. This process linked to inflammation has many features similar to the cytokine signaling of metabolic syndrome of obesity and its role in type 2 diabetes. Optimising the particular increased substrate requirements and over coming insulin resistance is considered central to affect outcome. The landmark Leuven study improved outcome with tight glycaemic control on the background of an intensive nutrition programme ^[4].

Recognising the altered and sometimes increased metabolic requirements is central to understanding why nutrition becomes so important. All the processes of inflammation, cell maintenance, healing and repair are dependent on  substrate provision that can come from mobilising limited stores or degrading existing structures in the absence of external provision. The myriad of lipid inflammatory mediators for instance are in part dependent on the character and potency of the long chain lipids previously ingested and incorporated into existing cell membranes. Therefore even the content of prior nutritional intake may affect the disease state. The provision of new lipid mixtures that perhaps better reflect substrate demands of our 10,000 year old genome is an exciting area of disease modification and nutritional genomics.

The catabolism of structural proteins occurs specifically to mobilize important amino acids to meet these altered requirements and occurs, unlike in starvation, with increased protein synthetic demands in many tissues particularly the immune system, liver and those involved in healing. The increased demand for glucose and glutamine for instance must come from protein breakdown and the huge increase in skeletal muscle catabolism is the most evident. Nutrient  provision is therefore struggling merely to keep pace with consumption and limit endogenous loss. With protein synthesis already stimulated amino acid and insulin provision has little ability to stimulate further and therefore there is on opportunity to catch up for missed feeding as in health and starvation? Consistency of nutrient delivery in this situation appears the most optimal and starting as soon as practical and continued for as longer as needed is important to give enough but not too much.

Is enteral nutrition always best?
Routes of delivery that can safely use the gastrointestinal tract will maintain intestinal organ function and the gut associated immunity. Studies of enteral nutrition (EN) consistently show in the less ill patients a reduced infectious morbidity compared with using parenteral nutrition (PN). Not delaying the start of enteral feeding in many patients appears advantageous but the overall risk and benefit is dictated by the presence of GI dysfunction which not only limits enteral nutrition delivery but increases morbidity and mortality of EN. However giving a patient only parenteral nutrition when the GI tract is completely functional prevents them from obtaining the advantages of enteral nutrition and at the same time exposes them to the risks of PN. Making an either or decision over EN or PN ignores the variability in GI dysfunction that occurs and ignores the metabolic requirement to delivery enough but not too much of the appropriate nutrients. Evidence shows that EN invariably results in underfeeding while PN carries the risk of overfeeding. The former often does not matter in the majority of well nourished patients in the short term but in the malnourished patient underfeeding may impact on survival over a long ICU stay. Overfeeding also must be avoided since it will only exacerbate the complications of the ICU form of metabolic syndrome and further increase insulin demand.

Is there any evidence that following good nutrition practice will improve outcome?
A 14 hospital cluster study from Canada, the ACCEPT study, showed that survival from intensive care was improved when an evidence based guideline for nutrition was followed and more nutrition was delivered more consistently. This was achieved by earlier introduction and more complete enteral nutrition delivery without any decline in the use of PN alone or in supplementation ^[5].

Safe Nutrition
Although EN is the mainstay of nutrition delivery within intensive care some have developed a blind faith in its benefits and a disregard of its risks. A few commentators even have a mistaken belief that parenteral nutrition (PN) is no longer required and that it is fraught with risks to the patients ^[6]. This has never been the case and a robust defence of PN within ICU nutrition support is published ^[7]. Sadly the indiscriminate use of PN or use of incomplete or unbalanced high glucose formulations particularly in North America was less a feature of practice in Europe where in addition we have used stable all-in-one formulations for decades.

A greater appreciation of the failings and risks of enteral nutrition delivery^[8] combined with improvements in PN formulation and use help explain why PN is not as risky as some have believed. There is only one level one study that correctly addresses the question of the choice in those patients where uncertainty exists over gastro-intestinal tolerance. This study suggests that EN may even carry a higher mortality risk ^[9] and contributes to meta-analyses and guidelines that have implied there was no overall difference in mortality rates ^[10]. A new detailed intention-to-treat analysis from nine studies comparing EN v PN used a component based approach to investigate the effect of trial quality ^[11]. This has shown a significant mortality benefit in favour of the use of PN (odds ratio, OR 0.51, 95% CI 0.27-0.97, p=0.04) confirming what this author has been saying ^[12]. This is despite EN use being associated with a significant reduction in infectious complications. The difference was less evident when the stat of nutrition support was not delayed. Since EN   is generally cheaper recommendations agree that EN is preferred where the gastrointestinal tract is intact and practical but the important decision is also to decide when it safe. When PN is necessary (as demonstrated by gastrointestinal) failure or complete intolerance of enteral nutrition delivery) the best evidence available recommends the use of  glutamine containing PN formulations as real outcome benefits have been described ^{[13, 14]}. The use of PN in   combination with EN understandably remains controversial since there is a paucity of data but there appears no harm. What studies exist have given PN from the outset and not started it once clear EN failure has been documented. The  latter is the accepted clinical position and means that PN should be considered depending upon the patient’s nutritional status and circumstances after 3 to 5 days once strategies to optimise EN have been exhausted.

Parenteral nutrition remains a valuable yet challenging weapon in our therapeutic armoury in the presence of gastro-intestinal feed intolerance or failure. However it should be used wisely and not indiscriminately since the majority of  ICU patients with a fully functional gastro-intestinal tract may usually be fed safely with enteral nutrition.

Reference

1. Giner M, Laviano A, Meguid MM, Gleason JR. In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists. Nutrition, 1996; 12:23-29.
2. Galanos AN, Pieper CF, Kussin PS, Winchell MT, Fulkerson WJ, Harrell FE Jr, Teno JM, Layde P, Connors AF Jr, Philips RS, Wenger NS. Relationship of body mass index to subsequent mortality among seriously ill hospitalized patients. SUPPORT Investigators. The Study to Understand Prognoses and Preferences for Outcome and Risks of Treatments. Critical Care Medicine. 1997; 25:1962-1968.
3. Villet S, Chiolero RL, Bollmann MD, Revelly J-P, Cayeux M-C, Delarue J, Berger MM, Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patient. Clinical Nutrition 2005.
4. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically patient. New Engl J Med 2001; 345:1359-1367.
5. Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ, for the Southwestern Ontario Critical Care Research Network. Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). CMAJ 2004; 170(2):197-204.
6. MarikPE, Pinsky M. Death by parenteral nutrition (2003) Intensive Care Med 29:867-869.
7. Varga P, Griffiths RD, Chiolero R, Nitenberg G, Leverve X, Pertkiewicz M, Roth E, Wernerman J, Pichard C, Preiser J-C. Is parenteral nutrition guilty? Intensive care Medicine 2003; 26:1861-1864.
8. Mentec H, Dupont H, Bocchetti M, Cani P, Ponche F, Bleichner G. Upper digestive intolerance during enteral nutrition in critically ill patients: Frequency, risk factors, and complications. Crit Care Med 2001; 29:1955-1961.
9. Woodcock NP, Zeigler D, Palmer D, Buckley P, Mitchell CJ, Macfie J. Enteral versus parenteral nutrition: a pragmatic study. Nutrition 2001; 17:1-12.
10. Heyland DK et al. Canadian clinical practice guidelines for nutrition support in Mechanically ventilated, critically ill adult patients. Journal of Parenteral and Enteral nutrition, 2003; 27:355-373.
11. Simpson F, Doig GS. Parenteral vs. Enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Medicine 2004 epub 10.1007/200134-004-2511-2.
12. Griffiths RD.Is parenteral nutrition really that risky in the intensive care unit? Curr Opin Clin Nutr Metab Care 2004; 7:175-181.
13. Griffiths RD, Allen KD, Andrews FJ, Jones C. Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection. Nutrition 2002; 18:546-552.
14. Goeters C, Wenn A, Mertes N, Wempe C, Van Aken H, Stehle P, Bone H-G. Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med 2002; 30:2032-2037.

From 
“The 11^th PENSA Congress” October 1-4, 2005,
Sheraton Grande Walkerhill Hotel, Seoul, Korea. 
Page 160-162